Protein Treatment Protects Against Alzheimer’s Disease Symptoms

A protein called klotho has been shown to protect against learning and memory deficits despite the accumulation of Alzheimer-related toxins in the brain, according to a new report in the Journal of Neuroscience.

Scientists from the Gladstone Institutes and the University of California, San Francisco tested klotho’s protective capacity by creating a mouse model of Alzheimer’s disease that produced higher levels of this protein throughout the body. Ordinarily, Alzheimer’s-model mice have cognitive deficits, abnormal brain activity, and premature death, but raising klotho levels ameliorated these problems. The cognition-enhancing effects of the protein were powerful enough to counteract the effects of Alzheimer-related toxins, whose levels were unchanged.

“It’s remarkable that we can improve cognition in a diseased brain despite the fact that it’s riddled with toxins,” says lead author Dena Dubal, MD, PhD, an assistant professor of neurology and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease at UCSF. “In addition to making healthy mice smarter, we can make the brain resistant to Alzheimer-related toxicity. Without having to target the complex disease itself, we can provide greater resilience and boost brain functions.”

Klotho’s benefits may be due to its effect on a certain type of neurotransmitter receptor in the brain, called NMDA, that is crucially involved in learning and memory. While Alzheimer’s impairs NMDA receptors, the mice with klotho elevation maintained normal receptor levels.

“The next step will be to identify and test drugs that can elevate klotho or mimic its effects on the brain,” says senior author Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and the Joseph B. Martin Distinguished Professor of Neuroscience at UCSF. “We are encouraged in this regard by the strong similarities we found between klotho’s effects in humans and mice in our earlier study. We think this provides good support for pursuing klotho as a potential drug target to treat cognitive disorders in humans, including Alzheimer’s disease.”